Both clades of the epidemic KPC-producing Klebsiella pneumoniae clone ST258 share a modified galactan O-antigen type

Szijártó, Valéria; Guachalla, Luis Miguel; Hartl, Katharina; Varga, Cecília; Banerjee, Prashant; Stojkovic, Katarina; Kaszowska, Marta; Nagy, Eszter; Łukasiewicz, Jolanta; Nagy, Gábor

doi:10.1016/j.ijmm.2015.12.002

Cited by 46 publications

(102 citation statements)

References 35 publications

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“…Moreover, both isolates were positive for the operon required for galactan-III synthesis that was recently described in the majority of ST258 clinical isolates [21]. …”

Section: Methodsmentioning

confidence: 87%

Differences in Inflammatory Response Induced by Two Representatives of Clades of the Pandemic ST258 Klebsiella pneumoniae Clonal Lineage Producing KPC-Type Carbapenemases

et al. 2017

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ST258-K. pneumoniae (ST258-KP) strains, the most widespread multidrug-resistant hospital-acquired pathogens, belong to at least two clades differing in a 215 Kb genomic region that includes the cluster of capsule genes. To investigate the effects of the different capsular phenotype on host-pathogen interactions, we studied representatives of ST258-KP clades, KKBO-1 and KK207-1, for their ability to activate monocytes and myeloid dendritic cells from human immune competent hosts. The two ST258-KP strains strongly induced the production of inflammatory cytokines. Significant differences between the strains were found in their ability to induce the production of IL-1β: KK207-1/clade I was much less effective than KKBO-1/clade II in inducing IL-1β production by monocytes and dendritic cells. The activation of NLRP3 inflammasome pathway by live cells and/or purified capsular polysaccharides was studied in monocytes and dendritic cells. We found that glibenclamide, a NLRP3 inhibitor, inhibits more than 90% of the production of mature IL-1β induced by KKBO1 and KK207-1. KK207-1 was always less efficient compared to KKBO-1 in: a) inducing NLRP3 and pro-IL-1β gene and protein expression; b) in inducing caspase-1 activation and pro-IL-1β cleavage. Capsular composition may play a role in the differential inflammatory response induced by the ST258-KP strains since capsular polysaccharides purified from bacterial cells affect NLRP3 and pro-IL-1β gene expression through p38MAPK- and NF-κB-mediated pathways. In each of these functions, capsular polysaccharides from KK207-1 were significantly less efficient compared to those purified from KKBO-1. On the whole, our data suggest that the change in capsular phenotype may help bacterial cells of clade I to partially escape innate immune recognition and IL-1β-mediated inflammation.

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“…Moreover, both isolates were positive for the operon required for galactan-III synthesis that was recently described in the majority of ST258 clinical isolates [21]. …”

Section: Methodsmentioning

confidence: 87%

Differences in Inflammatory Response Induced by Two Representatives of Clades of the Pandemic ST258 Klebsiella pneumoniae Clonal Lineage Producing KPC-Type Carbapenemases

et al. 2017

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“…The finding that some of the isolates tested were readily killed in human blood or serum was surprising to us, since bacteremia is relatively common (among individuals with infections caused by carbapenem-resistant K. pneumoniae isolates) and ST258 isolates whose genomes encode the same capsule polysaccharide subtype (e.g., cps-2) are genetically very similar (30,39). Previous studies have shown that the Klebsiella lipopolysaccharide (LPS) O antigen and/or the capsule polysaccharide contributes to resistance to the bactericidal activity of human serum (40)(41)(42)(43)(44)(45). Merino et al proposed that the deposition of complement C3b occurs too far from the membrane of serumresistant strains of K. pneumoniae, and thus, the C5b-C9 MAC fails to form (43).…”

Section: Survival Of K Pneumoniae In Bloodmentioning

confidence: 99%

Survival of Carbapenem-Resistant Klebsiella pneumoniae Sequence Type 258 in Human Blood

DeLeo

Kobayashi

Porter

et al. 2017

Antimicrob Agents Chemother

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Klebsiella pneumoniae is a prominent cause of nosocomial infections worldwide. Bloodstream infections caused by carbapenem-resistant K. pneumoniae, including the epidemic lineage known as multilocus sequence type 258 (ST258), are difficult to treat, and the rate of mortality from such infections is high. Thus, it is imperative that we gain a better understanding of host defense against this pathogen as a step toward developing novel therapies. Here we tested the hypothesis that the resistance of ST258 to bactericidal components of human blood, such as serum complement, is linked to virulence capacity in the context of bacteremia. There was significant variance in the survival of ST258 clinical isolates in heparinized human blood or normal human serum. The rate of survival of ST258 isolates in human blood was, in general, similar to that in normal human serum, suggesting a prominent role for complement (rather than leukocytes) in the healthy host defense against ST258 isolates and related organisms. Indeed, deposition of serum complement-the C5b to C9 (C5b-C9) membrane attack complex-onto the surface of ST258 isolates accompanied serum bactericidal activity. Human serum treated with pharmacological inhibitors of complement, depleted of antibody, or heated at 56°C for 30 min had significantly reduced or absent bactericidal activity. In contrast to heparinized blood from humans, that from BALB/c mice lacked bactericidal activity toward the ST258 isolates tested, but the virulence of these ST258 isolates in a mouse bacteremia model was inexplicably limited. Our data highlight the importance of the complement system in host defense against ST258 bacteremia, and we propose that there is the potential to enhance complement-mediated bactericidal activity using an antibody-based approach.

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“…In contrast to most Gram-negative bacteria, variability of K. pneumoniae O-antigens is currently limited to 9 major O-serotypes: O1, O2, O2ac, O3, O4, O5, O7, O8, O12 (Hansen et al, 1999) and a few subtypes within these serogroups (Kelly and Whitfield, 1996). However, the occurrence of modified or novel O-antigen structures has been forecasted recently (Follador et al, 2016; Szijarto et al, 2016). Since O-antigens are far less variable than CPS, Klebsiella LPS O-antigens have been suggested as potential target antigens for immunotherapy as an alternative to antibiotic treatment (Rukavina et al, 1997; Trautmann et al, 1997, 2004; Hsieh et al, 2014; Follador et al, 2016; Szijarto et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

“…It was shown previously for the O2 serotype that d -gal-I can be decorated by stoichiometric and non-stoichiometric addition of O-acetyl or terminal d -galactose (Kelly et al, 1995). Recent studies revealed the frequent occurrence of gal-I backbone RU decorated by the terminal α- d -Gal p residue, termed as d -galactan-III (gal-III), within the O2 serogroup and the genetic background for this modification has been identified (Szijarto et al, 2016). It was shown that conversion of gal-I to gal-III is encoded by gmlABC , which is carried adjacent to the gal-I-encoding rfb ( wb ) operon.…”

Section: Introductionmentioning

confidence: 99%

Identification of d-Galactan-III As Part of the Lipopolysaccharide of Klebsiella pneumoniae Serotype O1

et al. 2017

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Klebsiella pneumoniae is a Gram-negative, ubiquitous bacterium capable of causing severe nosocomial infections in individuals with impaired immune system. Emerging multi-drug resistant strains of this species and particularly carbapenem-resistant strains pose an urgent threat to public health. The lipopolysaccharide (LPS) O-antigen is the main surface antigen. It contributes to the virulence of this species and determines the O-serotype of K. pneumoniae isolates. Among the nine main O-serotypes of K. pneumoniae, O1-and O2-type pathogens are causative agents of over 50% of all infections. Serotype O1, the most common O-serotype, expresses complex LPS consisting of d-galactan-I (a polymer built of → 3)-β-d-Galf-(1 → 3)-α-d-Galp-(1 → repeating units) capped by d-galactan-II (built of [ → 3)-α-d-Galp-(1 → 3)-β-d-Galp-(1 →] repeating units). Galactan-I is present as the sole polymer in O2 serotype. Recently, in case of serotype O2, conversion of galactan-I to galactan-III (→ 3)-β-d-Galf-(1 → 3)-[α-d-Galp-(1 → 4)]-α-d-Galp-(1 →) was reported. Substitution of → 3)-α-d-Galp by a branching terminal α-d-Galp was dependent on the presence of the gmlABC operon and had a major impact on the antigenicity of the galactan polymer. Genetic analysis indicated that 40% of the O1 clinical isolates also carry the gmlABC locus; therefore we aimed to characterize the corresponding phenotype of LPS O-antigens. The presence of galactan-III among O1 strains was proven using galactan-III-specific monoclonal antibodies and confirmed by structural analyses performed using sugar and methylation analysis as well as classical and high-resolution magic angle spinning NMR spectroscopy. By using an isogenic mutant pair, we demonstrated that galactan-III expression was dependent on the presence of glycosyltransferases encoded by gmlABC, as was shown previously for the O2 serotype. Furthermore, the galactan-II structures in O1gml+ strains remained unaffected corroborating no functional interactions between the biosynthesis of galactan-III and galactan-II polymers.

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Both clades of the epidemic KPC-producing Klebsiella pneumoniae clone ST258 share a modified galactan O-antigen type

Cited by 46 publications

References 35 publications

Differences in Inflammatory Response Induced by Two Representatives of Clades of the Pandemic ST258 Klebsiella pneumoniae Clonal Lineage Producing KPC-Type Carbapenemases

Differences in Inflammatory Response Induced by Two Representatives of Clades of the Pandemic ST258 Klebsiella pneumoniae Clonal Lineage Producing KPC-Type Carbapenemases

Survival of Carbapenem-Resistant Klebsiella pneumoniae Sequence Type 258 in Human Blood

Identification of d-Galactan-III As Part of the Lipopolysaccharide of Klebsiella pneumoniae Serotype O1

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